Engineering error correcting dynamics in nanomechanical systems.

Nanomechanical oscillators are an alternative platform for computation in harsh environments. However, external perturbations arising from such environments may hinder information processing by introducing errors into the computing system. Here, we simulate the dynamics of three coupled Duffing oscillators whose multiple equilibrium states can be used for information processing and storage. Our analysis reveals that, within experimentally relevant parameters, error correcting dynamics can emerge, wherein the system's state is robust against random external impulses. We find that oscillators in this configuration have several surprising and attractive features, including dynamic isolation of resonators exposed to extreme impulses and the ability to correct simultaneous errors.

The positive impact of smoking on poor sleep quality is moderated by IGF1 levels in cerebrospinal fluid: a case-control study among Chinese adults.

Objective: Previous research indicates associations between cigarette smoking, insulin-like growth factor-1 (IGF1), and sleep disturbances. This study aimed to examine the association between smoking and sleep quality and investigate the moderating role of IGF1. Methods: This case-control study involved 146 Chinese adult males (53 active smokers and 93 non-smokers) from September 2014 to January 2016. Sleep quality and disturbances were evaluated using the Pittsburgh Sleep Quality Index (PSQI), which includes seven scales. Pearson correlation analysis and logistic regression analysis were utilized to examine the link between IGF1 levels in cerebrospinal fluid (CSF) and PSQI scores. The effect of IGF1 was assessed using the moderation effect and simple slope analysis, with adjustments made for potential confounders. Results: Active smokers exhibited significantly higher global PSQI scores and lower IGF1 levels in CSF compared to non-smokers. A significant negative correlation was observed between IGF1 and PSQI scores (â = -0.28, P < 0.001), with a stronger association in non-smokers (Pearson r = -0.30) compared to smokers (Pearson r = -0.01). Smoking was associated with higher global PSQI scores (â = 0.282, P < 0.001), and this association was moderated by IGF1 levels in CSF (â = 0.145, P < 0.05), with a stronger effect at high IGF1 levels (Bsimple = 0.402, p < 0.001) compared to low IGF1 levels (Bsimple = 0.112, p = 0.268). Four subgroup analysis revealed similar results for sleep disturbances (Bsimple = 0.628, P < 0.001), with a marginal moderation effect observed on subjective sleep quality (Bsimple = 0.150, P = 0.070). However, independent associations rather than moderating effects were observed between IGF1 and sleep efficiency and daytime disturbance. Conclusion: We provided evidence to demonstrate the moderation effect of IGF1 on the relationship between smoking and sleep in CSF among Chinese adult males.

Fenofibrate inhibits MOXD1 and PDZK1IP1 expression and improves lipid deposition and inflammation in mice with alcoholic fatty liver.

AIMS: Alcoholic liver disease (ALD) can develop into cirrhosis and hepatocellular carcinoma but no specific drugs are available. Fenofibrate is therapeutically effective in ALD, however, the exact mechanism remains unknown. We explored the hub genes of ALD and the role of fenofibrate in ALD. MAIN METHODS: The hub genes of ALD were screened by bioinformatics method, and their functional enrichment, signalling pathways, target genes and their correlation with immune microenvironment and pathogenic genes were analysed. We also analysed the binding affinity of fenofibrate to proteins of hub genes using molecular docking techniques, and the effects on hub gene expression, lipid deposition, oxidative stress and inflammation in the liver of National Institute on Alcohol Abuse and Alcoholism (NIAAA) model mice. The regulatory effects of fenofibrate on MOXD1 and PDZK1P1 were investigated after gene silencing of peroxisome proliferator-activated receptor-α (Ppar-α). KEY FINDINGS: Hub genes identified, including monooxygenase DBH-like 1 (MOXD1), PDZK1-interacting protein 1 (PDZK1IP1) and solute carrier 51 ß (SLC51B), are highly predictive for ALD. Hepatic MOXD1 and PDZK1IP1 expression was elevated in patients with ALD and NIAAA model mice, with no significant difference in SLC51B expression between the groups. Fenofibrate binds tightly to MOXD1 and PDZK1IP1, inhibits their hepatic expression independently of PPAR-α signalling, and ameliorates lipid deposition, oxidative stress and inflammatory responses in NIAAA model mice. SIGNIFICANCE: MOXD1 and PDZK1IP1 are key genes in ALD progression; fenofibrate improves liver damage in NIAAA model mice by downregulating their expression. Our findings provide insight for improving diagnostic and therapeutic strategies for ALD.

Clinical characteristics and homology analysis of Staphylococcus aureus from would infection at a tertiary hospital in southern Zhejiang, China.

OBJECTIVE: Staphylococcus aureus (S. aureus), especially Methicillin resistant S. aureus (MRSA), has been disseminated across communities and hospitals, associated with severe infections and organ failure. In order to understand the clinical epidemiological characteristics of S. aureus stains in the First Affiliated Hospital of Wenzhou Medical University in 2018, the prevalence and the drug resistance of S. aureus stains were investigated, for improving the clinical effective prevention and control of S. aureus infection. METHODS: A total of 105 S. aureus isolates were separated from wound infection of inpatients in the First Affiliated Hospital of Wenzhou Medical University in 2018, and the department distributions and drug resistance of the isolates were analyzed. The genotyping homology analysis was conducted through the random amplified polymorphic DNA typing (RAPD-PCR) coupled with NTSYS cluster analysis. RESULTS: Among the 105 strains of S. aureus, 31 isolates were MRSA. The prevalence of MRSA among inpatients in the Departments of Burn, Trauma, Orthopedics, Nephrology and Neurosurgery were 35.48%, 19.35%, 9.68%, 6.45%, and 29.03%, respectively. Among the 105 strains, 35.24% strains were the hospital-acquired infections (HAI) and 64.76% strains were community-acquired infections (CAI). DNA genotyping of the 105 S. aureus strains showed seventeen different groups, most of which were type I, type VII, type IX, and type VII, the others were scattered. CONCLUSION: This study highlights the prevalence of S. aureus strains in the First Affiliated Hospital of Wenzhou Medical University in 2018. The emergence and mutation of the strains should be closely monitored for the prevention and control of the S. aureus infection and transmission in the nosocomial settings.

SDC1-TGM2-FLOT1-BHMT complex determines radiosensitivity of glioblastoma by influencing the fusion of autophagosomes with lysosomes.

Rationale: Glioblastoma (GBM) is the most common and malignant primary brain tumor in adults. Radiotherapy has long been an important treatment for GBM. Despite recent advances in tumor radiotherapy, the prognosis of GBM remains poor due to radioresistance. Autophagy has been reported as a basic factor to prolong the survival of tumor under radiation stress, but the molecular mechanism of how autophagy contributes to GBM radioresistance was still lacking. Methods: We established radioresistant GBM cells and identified their protein profiles by Tandem mass tag (TMT) quantitative proteomic analysis, then chose the radioresistant genes based on the TMT analysis of GBM cells and differentially expressed genes (DEGs) analysis of GEO database. Colony formation, flow cytometry, qPCR, western blotting, mRFP-GFP-LC3, transmission electron microscopy, immunofluorescence, and co-IP assays were conducted to investigate the regulation mechanisms among these new-found molecules. Results: Syndecan 1 (SDC1) and Transglutaminase 2 (TGM2) were both overexpressed in the radioresistant GBM cells and tissues, contributing to the dismal prognosis of radiotherapy. Mechanically, after irradiation, SDC1 carried TGM2 from cell membrane into cytoplasm, and transported to lysosomes by binding to flotillin 1 (FLOT1), then TGM2 recognized the betaine homocysteine methyltransferase (BHMT) on autophagosomes to coordinate the encounter between autophagosomes and lysosomes. Conclusions: The SDC1-TGM2-FLOT1-BHMT copolymer, a novel member of the protein complexes involved in the fusion of lysosomes and autophagosomes, maintained the autophagic flux in the irradiated tumor cells and ultimately enhanced radioresistance of GBM, which provides new insights of the molecular mechanism and therapeutic targets of radioresistant GBM.

Photothermal biosensor for HPV16 based on strand-displacement amplification and gold nanoparticles using a thermometer as readout.

Gold nanoparticles (AuNPs) in aggregated state have a strong near infrared region (NIR) absorption and the causes a much stronger photothermal effect than that of the dispersed AuNPs. Strand-displacement amplification (SDA) can produce large amount of single-stranded DNA (ssDNA), which in turn effectively prevent AuNPs from aggregation. In this study, these characteristics had been applied to design a photothermal biosensor for human papilloma virus (HPV and HPV16 were chosen as model target) detection. In the absence of HPV16, AuNPs was in the aggregated state and large temperature rise can be detected after the irradiation by 808 nm laser. The presence of HPV16 triggers the SDA reaction with the help of Bst DNA polymerase and Nt.BstNBI nicking endonuclease resulting in the production of large amounts of ssDNA; this protects unmodified AuNPs from salt-induced aggregation. Therefore, AuNPs was in a dispersed state and the temperature change was not significant after the irradiation of 808 nm laser. The difference of the temperature changing can be applied for the quantitative detection of HPV16 using a thermometer as readout. The linear response range is 1.0 fM ~ 50 pM with a detection limit of 0.3 fM. The proposed method has been applied to detect HPV16 in clinical cervical sample and is competent for clinical analysis.

Attenuation of Experimental Autoimmune Hepatitis in Mice with Bone Mesenchymal Stem Cell-Derived Exosomes Carrying MicroRNA-223-3p.

MicroRNA-223-3p (miR-223-3p) is one of the potential microRNAs that have been shown to alleviate inflammatory responses in pre-clinical investigations and is highly encased in exosomes derived from bone mesenchymal stem cells (MSC-exosomes). MSC-exosomes are able to function as carriers to deliver microRNAs into cells. Autoimmune hepatitis is one of the challenging liver diseases with no effective treatment other than steroid hormones. Here, we examined whether MSC-exosomes can transfer miR-223-3p to treat autoimmune hepatitis in an experimental model. We found that MSC-exosomes were successfully incorporated with miR-223-3p and delivered miR-223-3p into macrophages. Moreover, there was no toxic effect of exosomes on the macrophages. Furthermore, treatments of either exosomes or exosomes with miR-223-3p successfully attenuated inflammatory responses in the liver of autoimmune hepatitis and inflammatory cytokine release in both the liver and macrophages. The mechanism may be related to the regulation of miR-223-3p level and STAT3 expression in the liver and macrophages. These results suggest that MSC-exosomes can be used to deliver miR-223-3p for the treatment of autoimmune hepatitis.

Magnetofluorescent nanohybrid comprising polyglycerol grafted carbon dots and iron oxides: Colloidal synthesis and applications in cellular imaging and magnetically enhanced drug delivery.

Multifunctional nanohybrids are attracting increasing attention for potential biomedical applications such as bioimaging and drug delivery due to their combined advantages of individual components. However, challenges in the improvement of their synthesis and colloidal stability to facilitate practical biomedical applications still remain. In this work, we report an efficient synthetic approach to fabricate magnetofluorescent nanohybrid (IO-PG-CD) comprising fluorescent carbon dots (CDs) and magnetic iron oxide nanoparticles (IOs) through polyglycerol (PG) mediated covalent linkage in aqueous media. CDs and IOs are first grafted with PG layer, and then functionalized with carboxyl and amino groups, respectively. The resulting CD-PG-COOH and IO-PG-NH2 handled as simple chemical compounds are integrated through EDC/NHS crosslinking to obtain the desired IO-PG-CD nanohybrid. The unprecedented hydrophilicity of PG layer endows IO-PG-CD nanohybrid with excellent colloidal stability in various physiological media, facilitating biomedical applications in vitro and in vivo. IO-PG-CD nanohybrid exhibits low cytotoxicity and its uptake by cells can be obviously enhanced by external magnetic attraction. The internalized IO-PG-CD nanohybrid emits multicolor fluorescence as observed by confocal fluorescence microscopy, demonstrating much better photostability than the nanoparticle labeled with organic dye. Taking advantage of enormous chelating carboxyl groups on the surface of IO-PG-CD nanohybrid, platinum-based anticancer drug was loaded on the surface (IO-PG-CD/Pt) through complexation and delivered into cancer cells in a magnetically enhanced manner, killing the cancer cells efficiently in vitro. Moreover, in vivo cancer therapy indicates that the external magnetic attraction also obviously improves the anticancer efficacy of IO-PG-CD/Pt in HeLa subcutaneous xenografts.

High fiber dietary and sodium butyrate attenuate experimental autoimmune hepatitis through regulation of immune regulatory cells and intestinal barrier.

Autoimmune hepatitis (AIH) is chronic autoimmune liver disease accompanied with the imbalance of Treg/Th17 and increased intestinal permeability. We investigated the effects of a high fiber diet and sodium butyrate on the Treg/Th17 and intestinal barrier function in an experimental autoimmune hepatitis. Intraperitoneal injection of hepatic antigen (S100) was used to induce experimental autoimmune hepatitis mice model and mice were divided into normal control, S100 model control, S100 plus high fiber diet and S100 plus sodium butyrate. Serum aminotransferases and liver histology were examined. Short chain fatty acids in feces were determined by HPLC. The ratio of CD4 + C25 + Foxp3+ Treg and CD4 + IL-17 + Th17 were evaluated by flow cytometry. Tight junction proteins Zonula ocluden, Occludin and Claudin-1 were used to assess intestinal barrier function, so does Escherichia coli protein in the liver. Mice fed with either high fiber diet or sodium butyrate showed significantly lower levers of serum aminotransferases and minor liver injury compared to that of model control. Moreover, the ratio of Treg/Th17 was significantly higher in high fiber diet and sodium butyrate fed mice than that in model control. Furthermore, high fiber diet and sodium butyrate significantly increased intestinal tight junction proteins and decreased Escherichia Coli protein in the liver. In conclusion, high fiber diet and sodium butyrate can attenuate development of autoimmune hepatitis through regulation of immune regulatory cells and intestinal barrier function.

BMSCs-derived miR-223-containing exosomes contribute to liver protection in experimental autoimmune hepatitis.

Autoimmune hepatitis is a chronic inflammatory disease in the liver with potential to the development of liver fibrosis. Recent evidences suggest that bone marrow derived mesenchymal stem cells (BMSCs) may exert its therapeutic activity through exosomes. Moreover, miR-223 is highly expressed in BMSCs and plays an important role in autoimmune diseases. Therefore, in this study, hepatoprotective role of BMSCs and miR-223 was investigated in both mice and hepatocytes. Liver antigen S100 was used to establish autoimmune hepatitis model in mice while LPS and ATP were used to establish cell injury model in hepatocyte. Before the experiments, BMSCs were infected with pre-miR-223 and transfected with miR-223 inhibitor respectively. Exosomes from bone marrow stem cells were isolated by ultracentrifugation. Liver injury was evaluated by serum levels of ALT and AST as well as liver histology. Inflammation and cell death were examined by inflammatory cytokines and lactase dehydrogenase respectively. Both BMSCs-exo and BMSCs-exomiR-223(+) significantly reversed either S100 or LPS/ATP induced injury in mice and hepatocytes. Meanwhile, the expressions of cytokines, NLRP3 and caspase-1 were also downregulated by BMSCs-exo and BMSCs-exomiR-223(+) at both protein and mRNA levels in mice and hepatocytes. Moreover, BMSCs-exomiR-223(-) reverses the effects of BMSCs-exo and BMSCs-exomiR-223(+) in mouse AIH and in hepatocytes. In conclusion, bone marrow stem cell derived exosomes can protect liver injury in an experimental model of autoimmune hepatitis and the mechanism could be related to exosomal miR-223 regulation of NLRP3 and caspase-1.

Sodium butyrate ameliorates S100/FCA-induced autoimmune hepatitis through regulation of intestinal tight junction and toll-like receptor 4 signaling pathway.

BACKGROUND AND AIM: Recent investigation revealed that dysbiosis in the gut flora and disruption of permeability of intestinal barrier are possible causes for the development of autoimmune hepatitis. Supplementation of sodium butyrate has been suggested to protect liver injury from disrupted permeability of small intestine. In current study, we employed S100/Freund's complete adjuvant induced autoimmune hepatitis to investigate therapeutic efficacy of sodium butyrate and its mechanism in the liver and upper small intestine. METHODS: C57BL/6 mice were employed and divided into three groups - control group (n=8), autoimmune hepatitis group (n=12) and autoimmune hepatitis with treatment of sodium butyrate group (n=12). Histological staining and western blot analyses were employed to evaluate liver and upper small intestine morphology and gene expression respectively. RESULTS: The findings revealed that S100/Freund's complete adjuvant caused liver injury and disruption of upper small intestine villi. Sodium butyrate attenuated the injuries and prevented migration of Escherichia coli into the liver. Moreover, the effect of sodium butyrate on protection of injuries of the liver and upper small intestine could be due to inhibition of toll-like receptor 4 signaling pathway, as well as its down-regulation of inflammatory cytokines - interleukin-6 and tumor necrosis factor-a. CONCLUSIONS: Sodium butyrate can prevent liver injury by maintaining the integrity of small intestine and inhibiting inflammatory response in S100/Freund's complete adjuvant induced autoimmune hepatitis.